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用于胃癌治疗的具有低毒性和高效性的自组装两亲性嵌段共聚物-阿霉素偶联纳米粒子。

Self-assembled amphiphilic copolymers-doxorubicin conjugated nanoparticles for gastric cancer therapy with low toxicity and high efficacy.

机构信息

Department of Gastroenterology, the First People's Hospital of Wenling, Wenling, China.

出版信息

J Biomater Sci Polym Ed. 2022 Dec;33(17):2202-2219. doi: 10.1080/09205063.2022.2100024. Epub 2022 Aug 8.

Abstract

Amphiphilic copolymers have long been utilized to turn hydrophobic anticancer drugs into nanoparticles administered to patients with cancer. A lack of stability in these monotherapies may be blamed for their poor clinical results in patients with cancer. We propose novel nanotherapies based on polymeric small prodrugs that preserve pharmacologic effectiveness while significantly reducing the toxicity of the fabricated drugs in animals to overcome this problem. Doxorubicin is attached to the end of the PLA fragments through a hydrolyzable ester bond utilizing methoxypolyethylene glycol--poly(d, l-lactic acid) (mPEG-PCL(2K)) with conjugates to mimic the self-assembly of colloidal nanotherapies. In a gastric cancer xenograft model, this nanotherapy displays a long-lasting suppression of tumor growth once a reasonable dosage is administered. Our findings imply that a toxic chemical and hydrophobic can be converted into therapeutic effective self-delivery nanotreatment.

摘要

两亲性共聚物长期以来一直被用于将疏水性抗癌药物转化为纳米颗粒,用于癌症患者的治疗。这些单一疗法的稳定性差可能是导致癌症患者临床效果不佳的原因。我们提出了基于聚合小分子前药的新型纳米疗法,这些前药在保持药物药理活性的同时,还能显著降低所制备药物在动物体内的毒性,从而克服这一问题。阿霉素通过可水解酯键连接到 PLA 片段的末端,利用甲氧基聚乙二醇-聚(DL-乳酸)(mPEG-PCL(2K))与缀合物模拟胶体纳米疗法的自组装。在胃癌异种移植模型中,一旦给予合理剂量,这种纳米疗法就能长时间持续抑制肿瘤生长。我们的研究结果表明,有毒化学物质和疏水性物质可以转化为治疗有效的自递药纳米治疗。

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